Identification

Name
Bufexamac
Accession Number
DB13346
Type
Small Molecule
Groups
Approved, Experimental
Description

Bufexamac is a non-steroidal anti-inflammatory drug (NSAID) under the market name Droxaryl, Malipuran, Paraderm and Parfenac. It is typically administered topically for the treatment of subacute and chronic eczema of the skin, including atopic eczema and other inflammatory dermatoses, as well as sunburn and other minor burns, and itching. It has also been used in suppositories in combination with local anaesthetics indicated for haemorrhoids. The use of bufexamac has been discontinued in Canada and the United States, which may be due to undetermined clinical efficacy and a high prevalence of contact sensitization [2]. Bufexamac was also withdrawn by the EMA in April 2010.

Structure
Thumb
Synonyms
  • 2-(p-Butoxyphenyl)-acetohydroxamic acid
  • 4-Butoxy-N-hydroxybenzeneacetamide
  • 4-Butoxyphenylacetohydroxamic acid
  • Acide p-butoxyphenylacethydroxamique
  • bufexamaco
  • bufexamacum
  • Bufexamic acid
  • p-Butoxyphenylacetohydroxamic acid
External IDs
CP 1044 J3 / CP-1044-J3
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Norfemac Cream - 5%Cream5 %TopicalHoechst Marion Roussel1995-12-311999-08-11Canada
Norfemac Ointment - 5%Ointment5 %TopicalHoechst Marion Roussel1995-12-311999-08-11Canada
Categories
UNII
4T3C38J78L
CAS number
2438-72-4
Weight
Average: 223.272
Monoisotopic: 223.120843411
Chemical Formula
C12H17NO3
InChI Key
MXJWRABVEGLYDG-UHFFFAOYSA-N
InChI
InChI=1S/C12H17NO3/c1-2-3-8-16-11-6-4-10(5-7-11)9-12(14)13-15/h4-7,15H,2-3,8-9H2,1H3,(H,13,14)
IUPAC Name
2-(4-butoxyphenyl)-N-hydroxyacetamide
SMILES
CCCCOC1=CC=C(CC(=O)NO)C=C1

Pharmacology

Indication

Indicated for the treatment of various skin conditions, such as atopic eczema and other inflammatory dermatoses.

Pharmacodynamics

Bufexamac is a topically-active anti-inflammatory agent that inhibits the cyclooxygenase enzyme. In cutaneous and deep experimental inflammation, topical administration of bufexamac exerted a dose-related anti-inflammatory effect [1]. In guinea pigs, bufexamax was shown to be more active than topical acetylsalicylic acid 5% or phenylbutazone 5% in delaying the local increase in temperature resulting from UV exposure [1]. Bufexamac is unlikely to have any effect on wound healing [1].

Mechanism of action

The full mechanism of action is unclear. It is proposed that bufexamac acts similarly to other non-steroidal anti-inflammatory drugs to inhibit prostaglandin biosynthesis in vitro, via inhibiting cyclo-oxygenase (COX) enzymes [1]. Systematically administered bufexamac may accumulate preferentially in the adrenal cortex of rats and may play a role in adrenal stimulation; however its topical anti-inflammatory action is likely to be independent of this effect [1].

TargetActionsOrganism
AProstaglandin G/H synthase 1
inhibitor
Human
AProstaglandin G/H synthase 2
inhibitor
Human
UHistone deacetylase 6
inhibitor
Human
UHistone deacetylase 10
inhibitor
Human
Absorption

Method of application affects the extent of cutaneous absorption [1]. Following rectal administration as suppositories, the systemic absorption was reported to be low [3].

Volume of distribution

No data available.

Protein binding

No data available.

Metabolism

No data available.

Route of elimination

Following topical administration of 5% bufexamac, the recovery in the urine was 3.5% of the applied dose within 144 hours [1]. Studies in healthy volunteers receiving an oral dose of 125 to 500 mg indicate that an average of 80% of the total dose is excreted in the urine within 48 hours [1].

Half life

No data available.

Clearance

No data available.

Toxicity

The LD50 in rat following oral and intraperitoneal administration is 3370 mg/kg and 805 mg/kg, respectively [MSDS]. Subcutaneous LD50 in mouse is >5000 mg/kg [MSDS]. Mild skin irritation was seen in rabbits following dermal application of 750 mg/30d(l) [MSDS]. Non-steroidal anti-inflammatory drug (NSAID) overdose may produce nausea, vomiting, indigestion and upper abdominal pain. Other effects may include drowsiness, dizziness, confusion, disorientation, lethargy [MSDS].

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(4R)-limoneneThe risk or severity of adverse effects can be increased when (4R)-limonene is combined with Bufexamac.
16-BromoepiandrosteroneThe risk or severity of adverse effects can be increased when Bufexamac is combined with 16-Bromoepiandrosterone.
19-norandrostenedioneThe risk or severity of adverse effects can be increased when Bufexamac is combined with 19-norandrostenedione.
5-androstenedioneThe risk or severity of adverse effects can be increased when Bufexamac is combined with 5-androstenedione.
AbciximabThe risk or severity of bleeding and hemorrhage can be increased when Bufexamac is combined with Abciximab.
AcebutololBufexamac may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of adverse effects can be increased when Aceclofenac is combined with Bufexamac.
AcemetacinThe risk or severity of adverse effects can be increased when Bufexamac is combined with Acemetacin.
AcenocoumarolBufexamac may increase the anticoagulant activities of Acenocoumarol.
AcetaminophenBufexamac may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
Food Interactions
Not Available

References

General References
  1. Brogden RN, Pinder RM, Sawyer PR, Speight TM, Avery GS: Bufexamac: a review of its pharmacological properties and therapeutic efficacy in inflammatory dermatoses. Drugs. 1975;10(5-6):351-6. [PubMed:1204506]
  2. Kranke B, Szolar-Platzer C, Komericki P, Derhaschnig J, Aberer W: Epidemiological significance of bufexamac as a frequent and relevant contact sensitizer. Contact Dermatitis. 1997 Apr;36(4):212-5. [PubMed:9165205]
  3. Glowania HJ, Hampl B: [Results of a study of the resorption of bufexamac following rectal administration]. Z Hautkr. 1988 Mar 21;63(3):211. [PubMed:3388925]
External Links
KEGG Drug
D01271
PubChem Compound
2466
PubChem Substance
347829293
ChemSpider
2372
BindingDB
50015144
ChEBI
31317
ChEMBL
CHEMBL94394
HET
A4Z
Wikipedia
Bufexamac
ATC Codes
M02AA09 — BufexamacM01AB17 — Bufexamac
PDB Entries
5bpp
MSDS
Download (352 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CreamTopical5 %
OintmentTopical5 %
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)153 to 155MSDS
water solubilityImmiscibleMSDS
Predicted Properties
PropertyValueSource
Water Solubility0.233 mg/mLALOGPS
logP2.09ALOGPS
logP1.97ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)8.86ChemAxon
pKa (Strongest Basic)-4.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area58.56 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity61.29 m3·mol-1ChemAxon
Polarizability24.58 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-00di-1090000000-f24ae0d85b1376dd6695
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-00di-5390000000-1064111002b4036cfbbb
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0aor-7900000000-789660a43653a49880b8
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-066r-5900000000-91ae318ee7bf4a0c8ebb
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-014i-4900000000-15c66804db050221c331
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-014i-3900000000-a41498b64629a3eda39c
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03di-0920000000-9e2d982e08339f818cf6
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0bt9-0900000000-435c1f72113403e534fa
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-0900000000-9de68224c670d85b5621
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-0900000000-496edd1f1dfb18e3bc93
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-1900000000-3e269c82012ba53557c2
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-2900000000-80c7b8b429b26dfbbfc6
MS/MS Spectrum - , positiveLC-MS/MSsplash10-08mi-0920000000-e2854ce6292c5d0a1c8c
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-4910100000-7ff98d442e9aa0a2f64d

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylacetamides. These are amide derivatives of phenylacetic acids.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Phenylacetamides
Direct Parent
Phenylacetamides
Alternative Parents
Phenoxy compounds / Phenol ethers / Alkyl aryl ethers / Hydroxamic acids / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Phenylacetamide / Phenoxy compound / Phenol ether / Alkyl aryl ether / Hydroxamic acid / Carboxylic acid derivative / Ether / Organopnictogen compound / Organooxygen compound / Organonitrogen compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
aromatic ether, hydroxamic acid (CHEBI:31317)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
Molecular Weight
68685.82 Da
References
  1. Brogden RN, Pinder RM, Sawyer PR, Speight TM, Avery GS: Bufexamac: a review of its pharmacological properties and therapeutic efficacy in inflammatory dermatoses. Drugs. 1975;10(5-6):351-6. [PubMed:1204506]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
Molecular Weight
68995.625 Da
References
  1. Brogden RN, Pinder RM, Sawyer PR, Speight TM, Avery GS: Bufexamac: a review of its pharmacological properties and therapeutic efficacy in inflammatory dermatoses. Drugs. 1975;10(5-6):351-6. [PubMed:1204506]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an impo...
Gene Name
HDAC6
Uniprot ID
Q9UBN7
Uniprot Name
Histone deacetylase 6
Molecular Weight
131418.19 Da
References
  1. Bantscheff M, Hopf C, Savitski MM, Dittmann A, Grandi P, Michon AM, Schlegl J, Abraham Y, Becher I, Bergamini G, Boesche M, Delling M, Dumpelfeld B, Eberhard D, Huthmacher C, Mathieson T, Poeckel D, Reader V, Strunk K, Sweetman G, Kruse U, Neubauer G, Ramsden NG, Drewes G: Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes. Nat Biotechnol. 2011 Mar;29(3):255-65. doi: 10.1038/nbt.1759. Epub 2011 Jan 23. [PubMed:21258344]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes.
Specific Function
Enzyme binding
Gene Name
HDAC10
Uniprot ID
Q969S8
Uniprot Name
Histone deacetylase 10
Molecular Weight
71444.08 Da
References
  1. Bantscheff M, Hopf C, Savitski MM, Dittmann A, Grandi P, Michon AM, Schlegl J, Abraham Y, Becher I, Bergamini G, Boesche M, Delling M, Dumpelfeld B, Eberhard D, Huthmacher C, Mathieson T, Poeckel D, Reader V, Strunk K, Sweetman G, Kruse U, Neubauer G, Ramsden NG, Drewes G: Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes. Nat Biotechnol. 2011 Mar;29(3):255-65. doi: 10.1038/nbt.1759. Epub 2011 Jan 23. [PubMed:21258344]

Drug created on June 23, 2017 14:40 / Updated on October 01, 2018 15:30